We plan to study and characterize the transport properties of lung epithelial barriers, and to determine their roles in the pathogenesis of alveolar pulmonary edema. Both alveolar and airway transport characteristics will be investigated. The hollow amphibian lung will be utilized as a model for alveolar epithelium. Airway epithelium will be studied by using primarily the posterior tracheal wall from dog or cat. The following biophysical characteristics will be determined: spontaneous potential difference, tissue resistance, active and passive fluxes of ions (including H ions), passive solute permeabilities and reflection coefficients (with estimation of equivalent pore size), active water movements, passive water permeability (due to hydrostatic and osomotic gradients), role of pinocytotic vesicles in transport, and mechanisms and pathways of water and solute transport across these epithelia. Particular attention will be paid to passive water and solute movements, since these fluxes are likely to be of primary importance in the formation of alveolar edema. Alveolar epithelial transport studies will be extended to mammalian lungs using two approaches: transport across a cultured monolayer of alveolar epithelial cells, and micropuncture of single alveoli. The properties of both epithelia will be determined under a number of physiological conditions, including variations in temperature, pH, (Ca ions), stretch, pulmonary capillary pressure, endogenous substance (e.g., ADH, epinephrine, acetylcholine, prolactin), and commonly used drugs (e.g., terbutaline, furosemide). Transport properties of lung epithelia will also be studied under a variety of pathological conditions often encountered in clinical situations. The effects of the following agents will be investigated: air pollutants (e.g., SO2, NO2, ozone), cigarette smoke, oxygen, metabolic poisons, infections, acid aspiration, and chemical agents known to damage lung tissue (oleic acid, ANTU). Understanding of the transport characteristics of airway and alveolar epithelium, studied independently, may help in the development of improved preventive and therapeutic maneuvers for alveolar pulmonary edema.